Regulation of immune cells by local-tissue oxygen tension: HIF1α and adenosine receptors

It should be appreciated that the oxygen tensions in inflamed tissues, and even in normal tissues, are usually low (that is, these tissues are hypoxic).The molecular mechanisms that ensure adaptation to hypoxia are operational in immune cells, thereby enabling immune surveillance in all tissue microenvironments and preventing 'safe shelters' for pathogens.Activated immune cells mainly rely on glycolysis, rather than on oxidative phosphorylation, as a source of energy.Hypoxia can regulate the activity of immune cells by promoting accumulation of adenosine and by stabilizing hypoxia-inducible factor 1α (HIF1α).Inhibition of HIF1 might have different effects in various types of immune cell. HIF1α deficiency in myeloid cells results in reduced inflammation. By contrast, in T cells, HIF1α is thought to be a negative regulator of activity.HIF1 is a promising therapeutic target for modulating immune responses. Inhibition or upregulation of HIF1α might induce or reduce inflammation depending on the type of immune response.